Urinary preparations of gonadotropins elicit neutralizing antibodies and ovarian refractoriness after 1-2 protocols. Follicular development was examined over 3 stimulations with recombinant human gonadotropins. Rhesus monkeys were pretreated for 7 days with a GnRH antagonist which continued during administration of either recombinant human FSH alone (n=6) or sequential treatment with r-hFSH (for 6 days) followed by R-hFSH q R-hLH (R-Plan A; n=6) for 3 stimulation cycles (C-1,2,3). When ultrasonography revealed follicles r4 mm diameter, R-hCG was given the next day. Follicles were aspirated 27 h post-hCG. The total number of follicles/animal and their size distribution, as well as the total number of oocytes collected/animal did not differ between cycles within treatments nor within cycles between treatments. Likewise, the percentage of mature oocytes collected at metaphase I and metaphase II was similar between C-1 and C-3 within R-hFSH and R-Plan A, respectively, as well as within cycles between treatments. Fertilization rates were comparable between C-1 and C-3 in R-hFSH, but increased from C-1 to C-3 in R-Plan A. Fertilization rates in C-1 were similar between groups, but following C-3 were less in R-hFSH relative to R-Plan A. Circulating antibodies to hFSH and hCG were absent after C-1 in both groups. At the end of C-3, modest levels of FSH antibodies were noted in 6 animals. Animals that were FSH antibody-positive after C-3 were also antibody-positive for hCG. Thus, 3 follicular stimulation cycles per macaque can be achieved with a protocol composed entirely of recombinant human gonadotropins.